1. Field of the Invention
This invention relates to methods of identifying and using compounds for stimulating nerve growth. In particular, this invention relates to complex carbohydrate compounds for stimulating nerve regrowth after injury.
2. Description of the Related Art
Nerve cell function depends upon appropriate contacts between the neuron and other cells in its immediate environment (U. Rutishauser, T. M. Jessell, Physiol. Rev. 68:819, 1988). These cells include specialized glial cells, oligodendrocytes in the central nervous system (CNS), and Schwann cells in the peripheral nervous system (PNS), which ensheathe the neuronal axon with myelin, which is an insulating structure of multi-layered membranes (G. Lemke, in An Introduction to Molecular Neurobiology, Z. Hall, Ed. [Sinauer, Sunderland, Mass., 1992], p. 281.).
Myelin is required for efficient nerve impulse conduction, but has other profound biological effects. The inability of nerves to regenerate after CNS injury in adults may be due largely to the axon's inability to grow when in contact with CNS myelin (P. Caroni, T. Savio, M. E. Schwab, Prog. Brain Res. 78:363, 1988; M. E. Schwab, J. P. Kapfhammer, C. E. Bandtlow, Annu. Rev. Neurosci. 16:565, 1993). Central nervous system injuries are particularly devastating because, unlike peripheral nerves, central nerves do not regenerate, so that central nervous system damage is usually permanent.
While CNS nerve cells have the capacity to regenerate after injury, they are inhibited from doing so by molecules normally found in their local environment. One such molecule is on myelin (Mukhopadhyay, G., et al. Neuron 13:757-767, 1994; McKerracher, L., et al. Neuron 13:805-811, 1994), and is referred to as myelin-associated glycoprotein (MAG). It would be desirable to identify molecular factors which interfere with the ability of MAG to inhibit nerve growth. Knowledge of those factors would form a basis for developing drug therapies to interfere with MAG's inhibitory effects, thus enhancing regeneration of nerves. The present invention provides a method to address these needs, and provides improved methods for treating nerve injury.